Production of alpha-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease

Xu He, Thomas Haselhorst, Mark von Itzstein, Daniel Kolarich, Nicolle H. Packer, Tracey M. Gloster, David J. Vocadlo, Lorne A. Clarke, Yi Qian, Allison R. Kermode

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Lysosomal storage diseases are a class of over 70 rare genetic diseases that are amenable to enzyme replacement therapy. Towards developing a plant-based enzyme replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis I, here we expressed alpha-L-iduronidase in the endosperm of maize seeds by a previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization, cellular fractionation and in situ RT-PCR demonstrate that the alpha-L-iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived protein bodies and to protein body-ER regions, respectively, using regulatory (5'- and 3'-UTR) and signal-peptide coding sequences from the gamma-zein gene. The maize alpha-L-iduronidase exhibits high activity, contains high-mannose N-glycans and is amenable to in vitro phosphorylation. This mRNA-based strategy is of widespread importance as plant N-glycan maturation is controlled and the therapeutic protein is generated in a native form. For our target enzyme, the N-glycan structures are appropriate for downstream processing, a prerequisite for its potential as a therapeutic protein.

Original languageEnglish
Article number1062
Pages (from-to)-
Number of pages9
JournalNature Communications
Volume3
DOIs
Publication statusPublished - Sept 2012

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